The hippo pathway provides novel insights into lung cancer and mesothelioma treatment

Liu, Xiaolan; Zuo, Rui; Ou, Wen‐Bin

doi:10.1007/s00432-018-2727-0

Cited by 14 publications

(13 citation statements)

References 108 publications

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“…Unfortunately, there is little information regarding the prognostic value of LATS2 expression in patients with PC. Several in vitro studies, using human cancer tissues, show that high expression of LATS2 is a significant predictor for better prognosis and longer survival periods in a variety of cancers, such as gastric cancer, lung cancer, and breast cancer 27,36,41 . We have no data on the relationship between the expression of LATS2 and survival periods, because the prognosis of patients with PC is generally good.…”

Section: Discussionmentioning

confidence: 98%

Pathological significance and prognostic role of LATS2 in prostate cancer

et al. 2021

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Background Large tumor suppressor 2 (LATS2) is an important regulator of the Hippo pathway and it plays crucial roles in cell survival and behaviors. Herein, we evaluated the pathological roles of LATS2 in prostate cancer (PC), for which very little information is available. Methods Cell proliferation, migration, and invasion in response to the siRNA‐mediated knockdown (KD) LATS2 expression were evaluated in two PC cell lines (LNCaP and PC3). The expression of LATS2 in specimens from 204 PC patients was investigated immunohistochemically, and the relationships between its expression and clinicopathological features, proliferation index (PI; measured using an anti‐KI‐67 antibody), and biochemical recurrence (BCR) were investigated. Results KD of LATS2 increased the growth, migration, and invasion in LNCaP cells and only increased migration in PC3 cells. The expression of LATS2 was negatively associated with the grade group, T, N, M stage, and PI. In addition, the expression of LATS2 was a useful predictor of the histological effects of neoadjuvant hormonal therapy and BCR‐free survival periods. A multivariate analysis model including clinicopathological features showed that negative expression of LATS2 had a significantly higher risk of BCR (odds ratio = 2.95, P < 0.001). Conclusions LATS2 acts as a tumor suppressor in PC. LATS2 expression is a useful predictor for BCR. LATS2‐related activities are possibly dependent on the androgen‐dependency of PC cells. Therefore, we suggest that LATS2 could be a potential therapeutic target and a useful predictor for outcome in patients with PC.

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Section: Discussionmentioning

confidence: 98%

Pathological significance and prognostic role of LATS2 in prostate cancer

et al. 2021

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“…It is known that the overexpression of STK3 can reduce the proliferation, migration, and invasion of glioblastoma and pancreatic cancer [ 24 , 25 ]. In nonsmall cell lung cancer tissues, the overexpression of STK3 can reduce the invasion and metastasis ability of lung cancer cells and promote lung cancer cell apoptosis [ 26 ]. Similarly, in the present study, we found that the overexpression of STK3 inhibits the invasion, proliferation, and metastasis of ovarian cancer cells and promotes their apoptosis.…”

Section: Discussionmentioning

confidence: 99%

STK3 Suppresses Ovarian Cancer Progression by Activating NF-κB Signaling to Recruit CD8+ T-Cells

Wang

Zhang

et al. 2020

Journal of Immunology Research

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Serine/threonine protein kinase-3 (STK3) is a critical molecule of the Hippo pathway but little is known about its biological functions in the ovarian cancer development. We demonstrated the roles of STK3 in ovarian cancer. Existing databases were used to study the expression profile of STK3. STK3 was significantly downregulated in OC patients, and the low STK3 expression was correlated with a poor prognosis. In vitro cell proliferation, apoptosis, and migration assays, and in vivo subcutaneous xenograft tumor models were used to determine the roles of STK3. The overexpression of STK3 significantly inhibited cell proliferation, apoptosis, and migration of ovarian cancer cells in vitro and tumor growth in vivo. Bisulfite sequencing PCR analysis was performed to validate the methylation of STK3 in ovarian cancer. RNA sequencing and gene set enrichment analysis (GSEA) were used to compare the transcriptome changes in the STK3 overexpression ovarian cancer and control cells. The signaling pathway was analyzed by western blotting. STK3 promoted the migration of CD8+ T-cells by activating nuclear transcription factor κB (NF-κB) signaling. STK3 is a potential predictor of OC. It plays an important role in suppressing tumor growth of ovarian cancer and in chemotaxis of CD8+ T-cells.

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“…Recent advances in understanding the components and functional implications of the Hippo pathway indicate its roles in tumorigenesis, tissue regeneration, organ development and stem cell self‐renewal (Park et al., 2018). The Hippo signalling pathway has also been implicated in playing pivotal roles in lung cancer pathogenesis, including multidrug resistance and tumour development (Liu, Zuo, & Ou, 2018). Taking in vivo xenograft and in vitro cell culture approaches, Liu et al.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐188 inhibits biological activity of lung cancer stem cells through targeting MDK and mediating the Hippo pathway

Yang

Wang

Chen

et al. 2020

Experimental Physiology

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MicroRNAs (miRNAs) have been implicated in lung cancer and reported as new promising diagnostic and therapeutic tools for cancer control. Here, we investigated the action of microRNA-188 (miR-188) in lung cancer stem cells. We first tested miR-188 expression in clinical samples of lung cancer patients, and a low expression profile of miR-188 was found. Next, we analysed the role of miR-188 in lung cancer stem cells with cell growth assays. To verify the in vitro results, we used a xenograft model to validate the capability of miR-188 in tumorigenesis. Overexpression of miR-188 reduced viability and metastasis of cancer stem cells. Similar results were reproduced in vivo, where overexpression of miR-188 retarded tumour growth in mice. We also identified MDK as a target of miR-188, and overexpression of MDK was found in lung cancer samples. Overexpressed MDK promoted the malignant behaviours of lung cancer stem cells. In addition, the Hippo pathway was found to be inactivated in lung cancer tissues, presenting as increased levels of YAP and TAZ. Suppression of the Hippo pathway also enhanced lung cancer stem cell activity and promoted the growth of xenograft tumours. To sum up, our results reveal that miR-188 inhibits the malignant behaviours of lung cancer stem cells and the growth of xenograft tumours. This study might offer new insights into gene-based therapies for cancer. K E Y W O R D S biological activity, Hippo pathway, lung cancer, MDK, microRNA-188, tumour stem cells 1 INTRODUCTION Lung cancer is one of the most prevalent tumours around the world and a main contributor to cancer-related death, among which non-small cell lung cancer (NSCLC) is the main type of lung cancer, accounting for 80-85% of all cases (Qiang et al., 2020). The pathogenesis of lung cancer is multifactorial, including both environmental and genetic factors, and the occurrence of lung cancer is associated with the modulation of tumour suppressor genes and oncogenes (Yu et al., 2020). In view of the insidious onset of lung cancer, most patients are in an advanced stage at the time of first diagnosis, rendering treatment difficult (Zhang, This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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The hippo pathway provides novel insights into lung cancer and mesothelioma treatment

Cited by 14 publications

References 108 publications

Pathological significance and prognostic role of LATS2 in prostate cancer

Pathological significance and prognostic role of LATS2 in prostate cancer

STK3 Suppresses Ovarian Cancer Progression by Activating NF-κB Signaling to Recruit CD8+ T-Cells

MicroRNA‐188 inhibits biological activity of lung cancer stem cells through targeting MDK and mediating the Hippo pathway

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